Literature DB >> 28743165

Prognostic factors and survival outcomes in patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era: Cohort study of 477 patients.

Preetesh Jain1, Hagop M Kantarjian1, Ahmad Ghorab1, Koji Sasaki1, Elias J Jabbour1, Graciela Nogueras Gonzalez2, Rashmi Kanagal-Shamanna3, Ghayas C Issa2, Guillermo Garcia-Manero1, Devendra Kc1, Sara Dellasala1, Sherry Pierce1, Marina Konopleva1, William G Wierda1, Srdan Verstovsek1, Naval G Daver1, Tapan M Kadia1, Gautam Borthakur1, Susan O'Brien1, Zeev Estrov1, Farhad Ravandi1, Jorge E Cortes1.   

Abstract

BACKGROUND: Outcomes in patients with chronic myeloid leukemia in blast phase (CML-BP) are historically dismal. Herein, the authors sought to analyze the characteristics, prognostic factors, and survival outcomes in patients with CML-BP in the tyrosine kinase inhibitor (TKI) era.
METHODS: A total of 477 patients with CML-BP were treated with a TKI at some point during the course of their CML. Cox proportional hazard models identified characteristics that were predictive of survival. Overall survival and failure-free survival were assessed. Optimal cutoff points for specific parameters were identified using classification and regression tree (CART) analysis.
RESULTS: The median age of the patients was 53 years (range, 16-84 years) and 64% were male. Approximately 80% of patients initially were diagnosed in the chronic phase of CML at a median of 41 months (range, 0.7-298 months) before transformation to CML-BP. De novo CML-BP occurred in 71 patients. Approximately 72% of patients received TKI therapy before CML-BP. The initial therapy for CML-BP included a TKI alone (35%), a TKI with chemotherapy (46%), and non-TKI therapies (19%). The median overall survival was 12 months and the median failure-free survival was 5 months. In multivariate analysis, myeloid immunophenotype, prior TKI, age ≥58 years, lactate dehydrogenase level ≥1227 IU/L, platelet count < 102 K/μL, no history of stem cell transplantation, transition to BP from chronic phase/accelerated phase, and the presence of chromosome 15 aberrations predicted for a significantly increased risk of death. Achievement of major hematologic response and/or complete cytogenetic response to first-line treatment was found to be predictive of better survival. The combination of a TKI with intensive chemotherapy followed by stem cell transplantation appeared to confer the best outcome.
CONCLUSIONS: Patients with CML-BP continue to pose a therapeutic challenge, have dismal outcomes, and require newer treatment approaches. Cancer 2017;123:4391-402.
© 2017 American Cancer Society. © 2017 American Cancer Society.

Entities:  

Keywords:  blast phase (BP); bosutinib; chronic myeloid leukemia (CML); dasatinib; imatinib; nilotinib; ponatinib; tyrosine kinase inhibitors (TKI)

Mesh:

Substances:

Year:  2017        PMID: 28743165      PMCID: PMC5673547          DOI: 10.1002/cncr.30864

Source DB:  PubMed          Journal:  Cancer        ISSN: 0008-543X            Impact factor:   6.860


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